Metformin and Muscle in Insulin-resistant Older Veterans

Prediabetes Clinical Trial

— M&M  

Official title:

Metformin and Muscle in Insulin-resistant Older Veterans

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01804049
• Other study ID #: CLIN-019-12S
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: April 8, 2014
• Est. completion date: August 31, 2018

Study information

• Verified date: February 2020
• Source: VA Office of Research and Development
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

Sarcopenia is the loss of muscle mass, strength and function with aging and is associated with increased disability, falls and fractures. Older adults with diabetes and prediabetes are insulin resistant and have a higher risk of developing sarcopenia. This study examines the use of metformin, an antidiabetic drug, for preventing the development of sarcopenia in older adults with prediabetes.

Description:

The proposed study utilizes clinical and translational research approaches to study sarcopenia. Sarcopenia is common in older adults and is associated with decreased strength, increased disability, falls and fractures. There are currently few interventions to prevent or treat sarcopenia and a poor understanding of the mechanisms for sarcopenia. Given the growing number of Veterans over the age of 65, studies to prevent sarcopenia and resulting disability are important for the health, independence and well-being of this population. The investigators' preliminary studies have shown that older adults with diabetes have an accelerated loss in muscle mass and gait speed, except when treated with metformin. Older adults with prediabetes also have a greater decline in muscle mass and higher incidence of disability. Therefore, this study further investigates these findings by addressing the following aims: (1) to determine whether metformin can prevent the loss in muscle mass and physical performance and (2) to examine changes in muscle histologic characteristics associated with metformin treatment in older adults with prediabetes.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: August 31, 2018
• Est. primary completion date: August 31, 2018
• Accepts healthy volunteers: No
• Gender: All
• Age group: 65 Years and older

Eligibility

Inclusion Criteria:

• The investigators will enroll 120 sedentary, weight-stable, ambulatory Veterans aged 65 years and older with prediabetes identified with fasting glucose values 100 mg/dL or greater but under 126 mg/dL with no use of diabetes medications.

• Participants must demonstrate that they are able to ambulate 400 meters without assistance.

Exclusion Criteria:

• Chronic medical conditions affecting muscle mass or function like active non-skin cancer and hypogonadism

• Medications affecting muscle mass or function like glucocorticoids and androgen/antiandrogens

• Contraindications to metformin such as renal dysfunction defined as creatinine >= 1.5 mg/dL for men or >=1.4 mg/dL for women or estimated glomerular filtration rate (eGFR)<60 mL/min; liver dysfunction defined as alanine aminotransferase (ALT)>48 U/L, aspart aminotransferase (AST)>41 U/L or alkaline phosphatase (AlkPhos)>141 U/L; B12 deficiency defined as B12 level <180 pg/dL; congestive heart failure; known hypersensitivity to metformin; excessive alcohol intake (average of 2 or more alcoholic beverages/day over a month)

For the muscle biopsy substudy, additional exclusion criteria include:

• Conditions that include bleeding risk such as the use of warfarin, clopidogrel/ticlopidine, aggrenox, dabigatran or anagrelide; laboratory results showing platelets<150 billion/L or international normalized ratio (INR)>1.2 or activated partial thromboplastin time (aPTT)>36 seconds

• Allergy to lidocaine

Related Conditions & MeSH terms

• Prediabetes
• Prediabetic State

Intervention

Drug:
• metformin
Metformin will be given at a dose of 850 mg orally once daily for 1 month with titration up to 850 mg orally twice daily for the remainder of the study.
• placebo
One placebo capsule by mouth once daily for 1 month followed by one placebo capsule by mouth twice daily for the remainder of the study.

Locations

Country	Name	City	State
United States	VA Portland Health Care System, Portland, OR	Portland	Oregon

Sponsors (2)

Lead Sponsor	Collaborator
VA Office of Research and Development	Oregon Health and Science University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Total Lean Mass From Baseline	At baseline, 1, 2, and 3 year follow-up visits, participants will have whole body dual x-ray absorptiometry scans (DXA) with a Hologic QDR 4500W DXA scanner by a certified DXA operator to determine total body lean mass and appendicular lean mass (Kg). The changes in appendicular and total lean mass were calculated by determining the change from baseline to the three year data point. If participants withdrew from the study prior to collection of 3 year data, the final time point available was used.	3 years
Secondary	Change in Physical Performance - 400 Meter Walk Speed	At baseline, 1, 2, and 3 year follow-up visits, participants will have physical performance assessed using a 400 meter timed walk. We report the 400 meter timed walk speed as the change from baseline in seconds. The change in walk speed from baseline to the three year time point was used for analysis. For participants who withdrew from the study early, the walk speed from the final data point collected was used.	3 years
Secondary	Change in Muscle Characteristics	At baseline and 6 month follow-up visits, 32 subjects will undergo a muscle biopsy of the vastus lateralis muscle 15 cm above the patella using the modified Bergstrom technique under local anesthesia. The muscle biopsy specimens will be used for the histochemical and transcriptome analyses	6 months